Protective effects of hypothalamic beta-endorphin neurons against alcohol-induced liver injuries and liver cancers in rat animal models

Sengottuvelan Murugan, Nadka Boyadjieva, Dipak K. Sarkar

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods: Male rats received either BEP neuron transplants or control transplants in the hypothalamus and were randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results: Alcohol feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased the levels of triglyceride, hepatic stellate cell (HSC) activation factors, and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocellular carcinoma (HCC), collagen deposition, numbers of preneoplastic foci, levels of HSC activation factors and catecholamines, as well as inflammatory milieu and increased the levels of natural killer cell cytotoxic factors in the liver. Conclusions: These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and HCC formation possibly via influencing the immune function.

Original languageEnglish (US)
Pages (from-to)2988-2997
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number12
DOIs
StatePublished - Dec 1 2014

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Keywords

  • Alcoholic Liver Disease
  • Hepatocellular Carcinoma
  • Natural Killer Cells
  • Neuroimmune System
  • Stress Hormones

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